[gmx-users] [gmx-user] RMSD analysis of protein-ligand complex

[Justin Lemkul]

On 12/26/19 9:05 AM, Quin K wrote:
> Thank you!
> This is the output I got from parachem.
> https://docs.google.com/document/d/180rWUj4XE-_OFBCVPsJajohNRKUYIClcP_V3cOer5qw/view
> Can this be used as it is?
>
> I used it as it is and did not validate or optimized further, could that be
> the reason why ligand got detached from binding site during MD simulation?

Possibly. The charge and dihedral penalties are not low enough to be 
considered sufficient without explicit validation using QM water 
interaction energy and a 1-D potential energy surface around the 
(potentially) problematic dihedral. It may be that the topology is fine, 
but as the header says, penalties between 10-50 cannot be trusted 
without proving the parameters are OK.

-Justin

> Thanks in advance!
> Regards
> Q
>
> On Wed, Dec 18, 2019 at 1:23 PM Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>> On 12/18/19 6:40 AM, Quin K wrote:
>>> I generated ligand topology using parachem website, I didn't do any
>>> adjustments after, just used it as it is.
>> What do the penalty scores tell you about the quality of the parameters?
>>
>> -Justin
>>
>>> On Tue, 17 Dec 2019, 1:11 pm Justin Lemkul, <jalemkul at vt.edu> wrote:
>>>
>>>> On 12/15/19 1:18 PM, Quin K wrote:
>>>>> Hi
>>>>> Thank you!!!
>>>>>
>>>>> Let's say during restraining of ligand, if I increased  the -fc value
>> to
>>>>> 10000 (i had 1000) or higher and equilibrated it for longer time like 1
>>>> or
>>>>> 2 ns (I had 100ps), would it help?
>>>> Possibly.
>>>>
>>>>> Also would  restraining the protein and ligand independently help?
>>>>> Or is generating a better ligand topology the only way to solve this
>>>> issue?
>>>>
>>>> It depends on how you validated the ligand topology. Do you have
>>>> evidence that it is of sufficiently high quality?
>>>>
>>>> -Justin
>>>>
>>>>> Thanks in advance.
>>>>> Regards
>>>>>
>>>>> On Sun, Dec 15, 2019 at 11:07 PM Justin Lemkul <jalemkul at vt.edu>
>> wrote:
>>>>>> On 12/15/19 11:47 AM, Quin K wrote:
>>>>>>> Hi All,
>>>>>>>
>>>>>>> Further to following email, i just noted that the ligand has detached
>>>>>> from
>>>>>>> binding site.
>>>>>>> Is there a way to prevent this from happening?
>>>>>>> It happened to me once before with the same complex.
>>>>>> If the ligand is dissociating on a time scale that it shouldn't (e.g.
>>>>>> you expect it should stay bound), that suggests the ligand topology is
>>>>>> insufficiently accurate, arising from interactions with the protein
>> that
>>>>>> are too weak and/or interactions with water that are too strong.
>>>>>>
>>>>>>> Doesn't boundary conditions prevent ligand from detaching from
>> binding
>>>>>> site
>>>>>>> in protein during MD simulation?
>>>>>> No, PBC does not do this. A periodic system contains copies of
>> whatever
>>>>>> is happening in the central image.
>>>>>>
>>>>>> -Justin
>>>>>>
>>>>>> --
>>>>>> ==================================================
>>>>>>
>>>>>> Justin A. Lemkul, Ph.D.
>>>>>> Assistant Professor
>>>>>> Office: 301 Fralin Hall
>>>>>> Lab: 303 Engel Hall
>>>>>>
>>>>>> Virginia Tech Department of Biochemistry
>>>>>> 340 West Campus Dr.
>>>>>> Blacksburg, VA 24061
>>>>>>
>>>>>> jalemkul at vt.edu | (540) 231-3129
>>>>>> http://www.thelemkullab.com
>>>>>>
>>>>>> ==================================================
>>>>>>
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>>>> --
>>>> ==================================================
>>>>
>>>> Justin A. Lemkul, Ph.D.
>>>> Assistant Professor
>>>> Office: 301 Fralin Hall
>>>> Lab: 303 Engel Hall
>>>>
>>>> Virginia Tech Department of Biochemistry
>>>> 340 West Campus Dr.
>>>> Blacksburg, VA 24061
>>>>
>>>> jalemkul at vt.edu | (540) 231-3129
>>>> http://www.thelemkullab.com
>>>>
>>>> ==================================================
>>>>
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>> --
>> ==================================================
>>
>> Justin A. Lemkul, Ph.D.
>> Assistant Professor
>> Office: 301 Fralin Hall
>> Lab: 303 Engel Hall
>>
>> Virginia Tech Department of Biochemistry
>> 340 West Campus Dr.
>> Blacksburg, VA 24061
>>
>> jalemkul at vt.edu | (540) 231-3129
>> http://www.thelemkullab.com
>>
>> ==================================================
>>
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>> Gromacs Users mailing list
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-- 
==================================================

Justin A. Lemkul, Ph.D.
Assistant Professor
Office: 301 Fralin Hall
Lab: 303 Engel Hall

Virginia Tech Department of Biochemistry
340 West Campus Dr.
Blacksburg, VA 24061

jalemkul at vt.edu | (540) 231-3129
http://www.thelemkullab.com

==================================================